Specific Aims: Simian immunodeficiency virus (SIV) infection of macaques provides the best non- human primate model for studying AIDS. We will utilize the SIV/macaque model to determine whether the generation of AIDS virus-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTL) can protect against, or alter the course of AIDS virus infection in vivo. Specifically, we will use in vitro binding and immunogenicity assays to identify multiple CTL and HTL epitopes derived from the SIV Mac 251, and restricted by Mamu A*01 and defined DRB alleles Lipopeptides and cDNA minigenes will be utilized to deliver epitopes the identified to rhesus macaques expressing the appropriate MHC types. Challenge studies will examine the prophylactic efficancy of immunization with these constructs, and we correlate each outcome with elicitation of specific HTL responses, CTL responses and potential appearance of viral escape mutants. PROPOSED COMMERCIAL APPLICATION: The overall focus of our research is to develop a vaccine for prevention and treatment HIV and AIDS infection. The proposed research will develop an adequate system for testing the multi epitope approach to immunotherapy in non-human primates. SIV infection of macaques provides the best non-human primate model for studying AIDS.